Progess to Date

OncoMed has established numerous technologies for the detection, isolation and characterization of tumor initiating cells using both in vitro and in vivo assays. We have tested over 150 antibodies in xenograft models derived directly from fresh human tumor specimens. These xenograft models have proven to be a powerful tool for characterizing the properties and response to therapy of tumor initiating cells. Limiting dilution assays, performed in conjunction with these models, has led to an understanding of the pathways critical to tumor initiating cells.

The ability to identify cancer initiating cells and understand the pathways critical to survival has resulted in the development of humanized monoclonal antibodies with significant antitumor activity in vivo. Our lead program is an antibody that binds with high affinity and selectivity to its target and completely blocks ligand-receptor binding. As a result, both the tumor initiating cells and the bulk tumor cell populations are reduced. Activity has been demonstrated with this antibody as a single agent and in combination with approved chemotherapy or biologic agents, using both treatment and prevention models. An IND filing and initiation of clinical trials with this antibody is expected in 2008. Additional antibodies to other targets have also been humanized and are expected to enter preclinical development in 2008.

Perspective

Cancer cells are not all equal in their ability to drive tumor growth and metastasis, or in their response to standard therapies. The most malignant of the cancer cells, the tumor initiating cells, or cancer stem cells, may now be identified by molecular markers. This has led to an understanding of the biologic pathways critical for the survival of these cells and the identification of targets that successfully decrease the tumor initiating cells.

The limitations of standard chemotherapy and radiotherapy treatment may be the result of the apparent resistance of tumor initiating cells to these forms of therapy. Treatment that decreases the size of the tumor, but fails to effectively target the tumor initiating cells, will have only a limited benefit.

The ability to now develop treatments that target the tumor initiating cells raises the possibility of a significant shift in cancer treatment and the potential for providing long term benefits for the patients with advanced solid tumors.